1.1 Understanding depression − key issues

Geoff Watts:

Last time we heard how low mood in the form of mild depression can actually be helpful. When life in one way or another is thwarting us the experience of depression can make us rethink our goals, can encourage us to scale back our ambitions or try following a different path. This isn’t always possible of course, or at least that’s how it seems. Either way, depression can become chronic and severe and of no benefit at all. All of us face setbacks that can disrupt our lives so you might begin to wonder why we don’t all get depressed. Psychologists like Dr Rebecca Elliott of the University of Manchester speak of people who don’t succumb to these events as having ‘resilience’.

Dr Rebecca Elliott:

In the context of mental health we think of resilience as how well somebody is able to adapt and function in the face of stressful or traumatic experiences.

Geoff Watts:

Two people who face a marriage break up, one person might get depressed, the other person might not and you’d say the person who didn’t was ‘resilient’.

Dr Rebecca Elliott:

Resilient to that particular stressful event. That’s right.

Geoff Watts:

I mean it’s a very useful thing to have. Is it widely distributed in the population? I mean, are most people resilient to some degree?

Dr Rebecca Elliott:

My instinct says it’s probably one of those occasions where we’re looking at a continuum where at one end of the continuum you have people who are very vulnerable, who in the face of quite low levels of stress or even potentially no stress at all will develop a mental health problem such as depression. Whereas at the other end of the continuum you have people who, life can deal an appalling hand, they can have all sorts of terrible stressful experiences, and yet remain positive and optimistic in the face of all that stress. And my instinct says most of us are somewhere in the middle, and we all potentially have a tipping point where enough stress, enough difficulties could cause us to have at least some degree of a problem.

Geoff Watts:

If resilience sounds more like a description than an explanation that’s exactly right. And that’s why Rebecca Elliott and her colleagues at the university are running a research project designed to find out what makes some people more able to cope than others. In essence, they’re comparing the brains of people with and without resilience. Although it so far has aroused only limited interest among depression researchers, resilience has already called the attention of those who work on post-traumatic stress disorder. And some of their insights, according to Bill Deakin, Professor of Psychiatry at Manchester University, are relevant to both conditions.

Professor Bill Deakin:

The three general ideas that we are interested in, are that firstly, some people may inherently be more sensitive to rewards in the environment. So, you know, experience in pleasurable events puts us in a good mood. And some people may need less of that to be in a good mood so they’re kind of more sensitive to rewarding or reinforcing events that occur. So that’s one aspect.

And then the second is that some people seem to be more flexible in how they solve problems, you know, we call is cognitive flexibility. So some people just seem to be more flexible and adaptable and creative about how they get out of their difficulties.

And then the third aspect is the emotional part of the brain. So we know that parts of the brain, particularly the middle parts of the brain, which seems to be a sort of central station for controlling anxiety and our responses to threat, and also responses to loss actually. That some people may be more sensitive, and what sort of loss will trigger off a big emotional response.

We’re trying to find people who appear to be very resilient to adversities of life and others who have been rather sensitive, and to see the mix of those three mechanisms, pleasure sensitivity, emotional sensitivity and cognitive flexibility. How that comes together and how it might relate to genes and, you know, whether it can be changed or not as well.

Geoff Watts:

So the characteristics of a brain which is resilient might be thought of in terms of their chemistry or in terms of their wiring and those things would possibly reflect their early experiences and their genetic inheritance?

Professor Bill Deakin:

That’s right. The two continuously interact and I think most genetic influences in depression are going to be like that.

Geoff Watts:

The Manchester researchers are working on the assumption that different states of mind, including vulnerability to depression, should correlate with different patterns of activity inside the brain. To explore them they’re using the scanning technique known as functional magnetic resonance imaging or fMRI. When volunteer subjects are slid in to the vast circular electromagnets on which these machines rely, it’s possible to image the structure of their brains. And, crucially, see which areas are functioning while they perform certain tasks. As I peered through the window that separates the control room from the instrument suite where the subjects are tested, Rebecca Elliott told me what they have to do.

Dr Rebecca Elliott:

They’re doing three different tasks while they’re in the scanner. One is an emotional memory task. We give them pictures to look at which are emotionally charged. So some are happy, positive pictures, some are sad and more negative pictures, and some are neutral pictures. And firstly, we ask them to look at them and try to remember them while their brain is being scanned. And then a little later we show them some of the same pictures again and ask them whether or not they’re pictures they’ve seen before. That’s probing emotional memory, how well people remember material that has an emotional component to it.

The second task we give them is what we call an emotional ‘go/no-go’ task. And in this people see a series of words flashing on the screen and they have to either ‘go’ (i.e. press a button), or ‘no-go’ (don’t press a button), depending on the emotional content of that word. So we have some blocks where they have to go to happy words and not go to sad words. Some blocks where we reverse that.

And then the final task we do is a task looking at their responses to rewards and punishments. And we actually use a task where they either win or lose money. And we look at how the brain responds when either they gain something, they win some money or when they lose some money.

Geoff Watts:

And in each case the hypothesis that you have is that people who have higher levels of resilience will show different pictures of activity from people who have low resilience?

Dr Rebecca Elliott:

That’s right. So at one end of our continuum, the ‘vulnerable’ people, we expect to show one pattern. The ‘resilient’ people at the other end, another pattern. And both of these will differ from, if you like, the average pattern that we see from people in the middle.

Aaron:

I’m generally a happy person, a busy person. I mean everybody has sort of stressful moments, I suppose, in their life, but day-to-day I would class myself as fairly happy. There’d be something wrong with you if you were happy all the time. But no, I certainly wouldn’t consider myself as ever having an episode of depression.

Geoff Watts:

Aaron, one of the people who volunteered to take part in the Manchester study. As you’ll have guessed he’s among those chosen for their resilience.

Aaron:

I suppose from my childhood when I first realised that I was gay, and lived with that for a long time. That taught me to sort of build up, I suppose, a sort of strong defence mechanism. And I didn’t actually come out to my parents or friends until I was much older. And so I lived with that for a long time. I suppose if you’ve gone through that situation whereby something is always in the background that is sort of fairly personal and stressful, I think perhaps that has made me deal with situations in a better way later on in life. I would say that my life can get fairly stressful at times, but it doesn’t seem to affect me in the way that it perhaps affects other people. I think it’s perhaps to do with my outlook on life. I do tend to think that if there is a problem that there’s always a solution, and I, kind of, think my way out of any problems. So it’s not that I don’t sort of think about any issues that might be going on in my life, but I always think that you can find a solution to any problems.

Professor Bill Deakin:

Well, I think that’s one aspect of being resilient. Certainly being optimistic, cheerful people. Think of your friends, you know, some of them are more cheerful and optimistic. There are some that don’t turn things over. Others turn things over a lot and ruminate about things. So using those sorts of aspects of personality I think we automatically think of some people as being resilient and tough, and others as being sort of sensitive, perhaps more liable to depression.

Geoff Watts:

Most of us do manage most of the time to stave off depression. So to understand resilience you also need a better understanding of ‘normality’, hence Bill Deakin and Rebecca Elliott’s attempts to peer inside the brain, looking for differences between subjects who do show resilience to depression and those who don’t.

Dr Rebecca Elliott:

Two particular regions that previous work have suggested may be important are a region of the brain called the amygdala, which we believe is important in processing emotional information. So we know, for example, that in people who are currently experiencing depression, the amygdala is over-responding to negative information. So, if you see a picture of a sad face, and you’ve currently got depression, your amygdala responds more strongly to that sad face. Another part of the brain we’re interested in is a part of the prefrontal cortex. And the prefrontal cortex is important in our cognitive performance, and to some extent in controlling our emotions. So regions of the prefrontal cortex will tend to inhibit the functions of regions like the amygdala. And we see this imbalance in depression, and in other emotional disturbances, and our hypothesis is that we’ll see, if anything, the opposite pattern in people who are resilient. Our early data suggests that people who are more resilient are more likely to recognise happy faces and less likely to recognise sad or fearful faces. We’ve also shown that people, exactly in line with what we hypothesise, the more resilient somebody is, the better they remember positive words and positive pictures.

Geoff Watts:

In the last few decades more and more hopes have been pinned on neuroscience as the means by which we’ll get to grips with mental health problems. But there are those who urge caution in this approach. One such is Professor Randolph Nesse of the University of Michigan. He tries to make sense of illness including depression by studying its evolutionary origins. It was he who explained in our last programme why mild depression may be beneficial. So what does he think of a ‘neuroscientific’ approach?

Professor Randolph Nesse:

A full understanding of anything in biology requires knowing every detail of the mechanism, and also how that mechanism came to be, and how it might be useful. And I have grand hopes along with most everybody else in psychiatry who is sensible that we will find specific brain abnormalities, or I should say differences, that account for why some people are more vulnerable to depression than other people who are less vulnerable to depression. However, I do see some neuroscientists acting as if the entire solution is going to be found in finding specific brain abnormalities. And it’s been very discouraging to actually look at what we’ve discovered over the past 20 years. Is there anything that can distinguish a brain of someone who has depression from a brain of someone who does not have depression? No. Not the brain scan, not the brain cutting, not the microscopic examination, not the hormones, not the neurotransmitters. There are some differences which are good clues, important clues. But our hope that we would find something specific like we find with multiple sclerosis or something has been completely dashed. It turns out depression is not in one place or one neurotransmitter. It’s distributed in systems, and those systems aren’t there just to make us depressed because it’s a problem. They’re there because the capacity for mood is useful.

Geoff Watts:

The hope of the Manchester team is, of course, that whatever insights they glean about the nature of resilience will offer ways of improving or better targeting existing treatments to prevent depression from taking hold. They’re aiming to build on what’s already done. Professor Deakin.

Professor Bill Deakin:

I mean, we do try and promote the resilience against recurrence of depression. And a lot of psychological therapies are based around that. So there’s quite good evidence that cognitive behavioural therapy, different psychological approaches, interpersonal psychotherapy, for example, a powerful technique, is a good way of reducing the chance of having a further episode if you’ve had depression. So by having depression you’re, kind of, shown to be perhaps a vulnerable person, not a resilient person.

Better psychological approaches could be devised, and enhanced by new kinds of medication that promote learning. And the combination may be particularly powerful in preventing relapse from depression. Because once you’ve had depressive illness the chance of having another one is very substantially increased over the general population. So it’s an important issue. And so that’s where we move out of society and in to the clinical situation. People who have had depression trying to promote resilience mechanisms to stop it happening again because we know it’s a big risk.

You might be able to in the future make a sort of a neuroscientific diagnosis so you get a readout of perhaps a simplified form of a scan or some EEG. Or you might get a sort of neuroscientific profile of what the particular problem is. So, in this individual, this individual got depressed because their reward mechanisms were completely fused, and actually from the emotional processing point of view and from the cognitive flexibility point of view they’re fine. So the target of therapy has to be on sort of promoting ability to respond to reward and the target might be something else. So that would really tailor make the therapy that you would have to reduce the chance of you having a second episode of depression.

Geoff Watts:

While cautious about the concept of resilience and the methods being used to study it, he applauds the intention and in particular the attempt to compare people who do get depressed with those who don’t.

Professor Randolph Nesse:

This is one of the wonderful things that’s come from positive psychology is studying not just people who have severe problems, but the people who don’t have problems despite being exposed to very dire circumstances either early in life or in adulthood. And this is very important research. We need to know how people differ and why some people just can get through things that other people cannot.

The difficulty though, is assuming that resilience is always good. Resilience is wonderful and especially in modern life where low mood, I think, is probably less useful than it used to be. The more resilient you are, up to a point at least, the better. But I really think it’s terribly important to try to, you know, be sympathetic towards people with depression not just as people with diseases who are somehow less able, and less fit than others but with people who have advantages as well as disadvantages.